CAY10410
(Synonyms: 9,10dihydro15deoxyΔ12,14PGJ2, 9,10dihydro15deoxyΔ12,14Prostaglandin J2) 目录号 : GC40384A less electrophilic, isosteric analog of 15-deoxy-D12,14-PGJ2
Cas No.:596104-94-8
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
CAY10410 is an analog of prostaglandin D2/prostaglandin J2 (PGD2/PGJ2) with structural modifications intended to give it PPARγ ligand activity and resistance to metabolism. 15-deoxy-δ12,14-PGJ2 has been shown to be a potent ligand for PPARγ. Metabolism of the cyclopentenone prostaglandins PGA2, PGJ2, and δ12-PGJ2 occurs via glutathione addition across the α,β unsaturated enone. CAY10410 was designed as an analog of the PPARγ-binding prostaglandins which could not undergo this conjugation reaction. In human neuroblastoma SH-SY5Y cells, CAY10410 was not cytotoxic at up to 25 µM. It also failed to covalently modify thioredoxin or induce oxidative stress at 50 µM.
| Cas No. | 596104-94-8 | SDF | |
| 别名 | 9,10dihydro15deoxyΔ12,14PGJ2, 9,10dihydro15deoxyΔ12,14Prostaglandin J2 | ||
| Canonical SMILES | O=C1/C([C@@H](C/C=C\CCCC(O)=O)CC1)=C/C=C\CCCCC | ||
| 分子式 | C20H30O3 | 分子量 | 318.5 |
| 溶解度 | DMF: 100 mg/ml,DMSO: 20 mg/ml,Ethanol: 75 mg/ml,PBS (7.2): 2.7 mg/ml | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.1397 mL | 15.6986 mL | 31.3972 mL |
| 5 mM | 0.6279 mL | 3.1397 mL | 6.2794 mL |
| 10 mM | 0.314 mL | 1.5699 mL | 3.1397 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
High-density lipoproteins suppress chemokines and chemokine receptors in vitro and in vivo
Arterioscler Thromb Vasc Biol 2010 Sep;30(9):1773-8.PMID:20702809DOI:10.1161/ATVBAHA.110.211342.
Objective: To investigate whether high-density lipoproteins (HDLs) suppress chemokine (CCL2, CCL5, and CX(3)CL1) and chemokine receptor (CCR2 and CX(3)CR1) expression, a mechanism for the atheroprotective properties of HDLs. Methods and results: Apolipoprotein (apo) E(-/-) mice were fed a high-fat diet for 12 weeks. Before being euthanized, the mice received 5 consecutive daily injections of lipid-free apoA-I, 40 mg/kg, or saline (control). The injection of apoA-I reduced CCR2 and CX(3)CR1 expression in plaques compared with controls (P<0.05). ApoA-I-injected mice had lower plasma CCL2 and CCL5 levels. Hepatic CCL2, CCL5, and CX(3)CL1 levels were also reduced (P<0.05). In vitro studies found that reconstituted HDL (rHDL) reduced monocyte CCR2 and CX(3)CR1 expression and inhibited their migration toward CCL2 and CX(3)CL1 (P<0.05). Preincubation with rHDL reduced CCL2, CCL5, and CX(3)CL1 expression in monocytes and human coronary artery endothelial cells. The stimulation of CX(3)CR1 with peroxisome proliferator-activated receptor gamma agonist CAY10410 was suppressed by preincubation with rHDL but did not affect the peroxisome proliferator-activated receptor gamma antagonist (GW9664)-mediated increase in CCR2. In monocytes and human coronary artery endothelial cells, rHDL reduced the expression of the nuclear p65 subunit, IkappaB kinase activity, and the phosphorylation of IkappaBalpha (P<0.05). Conclusions: Lipid-free apoA-I and rHDL reduce the expression of chemokines and chemokine receptors in vivo and in vitro via modulation of nuclear factor kappaB and peroxisome proliferator-activated receptor gamma.
Increased generation of cyclopentenone prostaglandins after brain ischemia and their role in aggregation of ubiquitinated proteins in neurons
Neurotox Res 2013 Aug;24(2):191-204.PMID:23355003DOI:10.1007/s12640-013-9377-4.
The cyclopentenone prostaglandin (CyPG) J₂ series, including prostaglandin J₂ (PGJ₂), Δ¹²-PGJ₂, and 15-deoxy-∆¹²,¹⁴-prostaglandin J₂ (15d-PGJ₂), are active metabolites of PGD₂, exerting multiple effects on neuronal function. However, the physiologic relevance of these effects remains uncertain as brain concentrations of CyPGs have not been precisely determined. In this study, we found that free PGD₂ and the J₂ series CyPGs (PGJ₂, Δ¹²-PGJ₂, and 15d-PGJ₂) were increased in post-ischemic rat brain as detected by UPLC-MS/MS with 15d-PGJ₂ being the most abundant CyPG. These increases were attenuated by pre-treating with the cyclooxygenase (COX) inhibitor piroxicam. Next, effects of chronic exposure to 15d-PGJ₂ were examined by treating primary neurons with 15d-PGJ₂, CAY10410 (a 15d-PGJ₂ analog lacking the cyclopentenone ring structure), or vehicle for 24 to 96 h. Because we found that the concentration of free 15d-PGJ₂ decreased rapidly in cell culture medium, freshly prepared medium containing 15d-PGJ₂, CAY10410, or vehicle was changed twice daily to maintain steady extracellular concentrations. Incubation with 2.5 μM 15d-PGJ₂, but not CAY10410, increased the neuronal cell death without the induction of caspase-3 or PARP cleavage, consistent with a primarily necrotic mechanism for 15d-PGJ₂-induced cell death which was further supported by TUNEL assay results. Ubiquitinated protein accumulation and aggregation was observed after 96 h 15d-PGJ₂ incubation, accompanied by compromised 20S proteasome activity. Unlike another proteasome inhibitor, MG132, 15d-PGJ₂ treatment did not activate autophagy or induce aggresome formation. Therefore, the cumulative cytotoxic effects of increased generation of CyPGs after stroke may contribute to delayed post-ischemic neuronal injury.
PPAR-γ ligands repress TGFβ-induced myofibroblast differentiation by targeting the PI3K/Akt pathway: implications for therapy of fibrosis
PLoS One 2011 Jan 6;6(1):e15909.PMID:21253589DOI:10.1371/journal.pone.0015909.
Transforming growth factor beta (TGFβ) induced differentiation of human lung fibroblasts to myofibroblasts is a key event in the pathogenesis of pulmonary fibrosis. Although the typical TGFβ signaling pathway involves the Smad family of transcription factors, we have previously reported that peroxisome proliferator-activated receptor-γ (PPAR-γ) ligands inhibit TGFβ-mediated differentiation of human lung fibroblasts to myofibroblasts via a Smad-independent pathway. TGFβ also activates the phosphatidylinositol 3 kinase/protein kinase B (PI3K/Akt) pathway leading to phosphorylation of Akt(S473). Here, we report that PPAR-γ ligands, 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid (CDDO) and 15-deoxy-(12,14)-15d-prostaglandin J(2) (15d-PGJ(2)), inhibit human myofibroblast differentiation of normal and idiopathic pulmonary fibrotic (IPF) fibroblasts, by blocking Akt phosphorylation at Ser473 by a PPAR-γ-independent mechanism. The PI3K inhibitor LY294002 and a dominant-negative inactive kinase-domain mutant of Akt both inhibited TGFβ-stimulated myofibroblast differentiation, as determined by Western blotting for α-smooth muscle actin and calponin. Prostaglandin A(1) (PGA(1)), a structural analogue of 15d-PGJ(2) with an electrophilic center, also reduced TGFβ-driven phosphorylation of Akt, while CAY10410, another analogue that lacks an electrophilic center, did not; implying that the activity of 15d-PGJ(2) and CDDO is dependent on their electrophilic properties. PPAR-γ ligands inhibited TGFβ-induced Akt phosphorylation via both post-translational and post-transcriptional mechanisms. This inhibition is independent of MAPK-p38 and PTEN but is dependent on TGFβ-induced phosphorylation of FAK, a kinase that acts upstream of Akt. Thus, PPAR-γ ligands inhibit TGFβ signaling by affecting two pro-survival pathways that culminate in myofibroblast differentiation. Further studies of PPAR-γ ligands and small electrophilic molecules may lead to a new generation of anti-fibrotic therapeutics.
15-Deoxy-delta 12,14-prostaglandin J2 biphasically regulates the proliferation of mouse hippocampal neural progenitor cells by modulating the redox state
Mol Pharmacol 2010 Apr;77(4):601-11.PMID:20086036DOI:10.1124/mol.109.061010.
The activity of neural progenitor cells (NPCs) is regulated by various humoral factors. Although prostaglandin (PG) D(2) is known to mediate various physiological brain functions such as sleep, its actions on NPCs have not been fully understood. In the process of investigating the effects of PGD(2) on NPCs, we found that 15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)), an endogenous metabolite of PGD(2), exhibits a novel regulation of the proliferation of NPCs derived from mouse hippocampus. 15d-PGJ(2) showed biphasic effects on epidermal growth factor-induced proliferation of NPCs; facilitation at low concentrations ( approximately 0.3 muM) and suppression at higher concentrations (0.5-10 microM) in vitro. 2-Chloro-5-nitrobenzanilide (GW9662), an inhibitor of peroxisome proliferator-activated receptor gamma, known to be a molecular target for 15d-PGJ(2), failed to abolish the effects of 15d-PGJ(2). 9,10-dihydro-15d-PGJ(2) (CAY10410), a structural analog of 15d-PGJ(2) lacking the electrophilic carbon in the cyclopentenone ring, did not show 15d-PGJ(2)-like actions. Treatment with 15d-PGJ(2) increased the levels of reactive oxygen species and decreased endogenous GSH levels. Furthermore, supplementation with a membrane-permeable analog of glutathione, GSH ethyl ester (2 mM), diminished the biphasic effects of 15d-PGJ(2). Finally, cell division in the dentate gyrus of postnatal mice was increased by injection of low-dose (1 ng i.c.v.) 15d-PGJ(2) and suppressed by high-dose (30 ng) 15d-PGJ(2). These results suggest that 15d-PGJ(2) regulates the proliferation of NPCs via its electrophilic nature, which enables covalent binding to molecules such as GSH.
15-Deoxy-delta(12,14)-prostaglandin J(2) down-regulates CXCR4 on carcinoma cells through PPARgamma- and NFkappaB-mediated pathways
Exp Cell Res 2007 Oct 1;313(16):3446-58.PMID:17707368DOI:10.1016/j.yexcr.2007.06.027.
The chemokine receptor CXCR4 plays a key role in the metastasis of colorectal cancer and its growth at metastatic sites. Here, we have investigated the mechanisms by which CXCR4 on cancer cells might be regulated by eicosanoids present within the colorectal tumor microenvironment. We show that prostaglandins PGE(2), PGA(2), PGD(2), PGJ(2) and 15dPGJ(2) each down-regulates CXCR4 receptor expression on human colorectal carcinoma cells to differing degrees. The most potent of these were PGD(2) and its metabolites PGJ(2) and 15dPGJ(2). Down-regulation was most rapid with the end-product 15dPGJ(2) and was accompanied by a marked reduction in CXCR4 mRNA. 15dPGJ(2) is known to be a ligand for the nuclear receptor PPARgamma. Down-regulation of CXCR4 was also observed with the PPARgamma agonist rosiglitazone, while 15dPGJ(2)-induced CXCR4 down-regulation was substantially diminished by the PPARgamma antagonists GW9662 and T0070907. These data support the involvement of PPARgamma. However, the 15dPGJ(2) analogue CAY10410, which can act on PPARgamma but which lacks the intrinsic cyclopentenone structure found in 15dPGJ(2), down-regulated CXCR4 substantially less potently than 15dPGJ(2). The cyclopentenone grouping is known to inhibit the activity of NFkappaB. Consistent with an additional role for NFkappaB, we found that the cyclopentenone prostaglandin PGA(2) and cyclopentenone itself could also down-regulate CXCR4. Immunolocalization studies showed that the cellular context was sufficient to trigger a focal nuclear pattern of NFkappaB p50 and that 15dPGJ(2) interfered with this p50 nuclear localization. These data suggest that 15dPGJ(2) can down-regulate CXCR4 on cancer cells through both PPARgamma and NFkappaB. 15dPGJ(2), present within the tumor microenvironment, may act to down-regulate CXCR4 and impact upon the overall process of tumor expansion.